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1.
Ren Fail ; 46(1): 2356708, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38803220

RESUMEN

As no unified treatment protocol or evidence yet exists for plasmapheresis without plasma, this study explored the outcomes of using 4% human albumin (ALB) solution as a replacement solution in patients undergoing plasma exchange for multiple myeloma (MM) patients with acute kidney injury (AKI). This study was prospectively registered (ChiCTR2000030640 and NCT05251896). Bortezomib-based chemotherapy plus therapeutic plasmapheresis (TPP) with 4% human ALB solution was assessed for three years in patients with MM aged >18 years, with AKI according to the Kidney Disease Improving Global Outcomes criteria, and without previous renal impairment from other causes. The primary endpoints were changes in renal function over 18 weeks and survival outcomes at 36 months. The secondary endpoints were the incidence of adverse reactions and symptom improvement. Among the 119 patients included in the analysis, 108 experienced renal reactions. The M protein (absolute changes: median -12.12%, interquartile ranges (IQRs) -18.62 to -5.626) and creatine (median -46.91 µmol/L, IQR -64.70 to -29.12) levels decreased, whereas the estimated glomerular filtration rate (eGFR) increased (median 20.66 mL/(min·1.73 m2), IQR 16.03-25.29). Regarding patient survival, 68.1% and 35.3% of patients survived for >12 and >36 months, respectively. The three symptoms with the greatest relief were urine foam, poor appetite, and blurred vision. All 11 patients (7.6%) who experienced mild adverse reactions achieved remission. In conclusion, in MM patients with AKI, plasma-free plasmapheresis with 4% human ALB solution and bortezomib-based chemotherapy effectively alleviated light chain damage to kidney function while improving patient quality of life.


Asunto(s)
Lesión Renal Aguda , Bortezomib , Tasa de Filtración Glomerular , Mieloma Múltiple , Plasmaféresis , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/terapia , Lesión Renal Aguda/terapia , Lesión Renal Aguda/etiología , Plasmaféresis/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Bortezomib/administración & dosificación , Bortezomib/uso terapéutico , Prueba de Estudio Conceptual , Albúmina Sérica Humana/análisis , Albúmina Sérica Humana/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Resultado del Tratamiento , Adulto , Terapia Combinada , Proteínas de Mieloma
2.
Int J Pharm ; 656: 124111, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38609057

RESUMEN

Methotrexate (MTX) is recognized as the golden standard for rheumatoid arthritis (RA) treatment. However, it can cause liver damage in long-term application. Although nanomedicines can target to inflamed sites, most of them tend to accumulate in liver. Glycyrrhizinic acid (GA) holds potential to reverse MTX-associated hepatotoxicity. The combination of GA and MTX might achieve a synergistic anti-inflammatory efficacy and reduced hepatotoxicity. As MTX and GA have totally different in vivo performance, it is necessary to co-encapsulate them in one carrier to coordinate their in vivo fates. Here, we co-delivered MTX and GA to arthritic joints using a human serum albumin-based nanoparticle (HSN). We found the dual drug-loaded albumin nanoparticles (HSN/MTX/GA) could preferentially distribute in inflamed joints, where GA can extend MTX retention by inhibiting the expression of efflux pumps for MTX, thereby exerting synergistic therapeutic effect. In liver tissues, GA was able to reverse the MTX-induced liver damage by activating anti-oxidant defense Nrf2/HO-1 and anti-apoptosis Bcl-2/Bax signaling. We offer a combinational strategy to effectively overcome the MTX-induced hepatotoxicity and enhance the anti-rheumatic efficacy simultaneously. Furthermore, we verified the underlying mechanism about how GA cooperated with MTX in vivo for the first time. Our findings can provide valuable insights for long-term treatment of RA.


Asunto(s)
Antirreumáticos , Enfermedad Hepática Inducida por Sustancias y Drogas , Ácido Glicirrínico , Metotrexato , Nanopartículas , Metotrexato/administración & dosificación , Animales , Antirreumáticos/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Ácido Glicirrínico/administración & dosificación , Ácido Glicirrínico/química , Ácido Glicirrínico/farmacología , Artritis Reumatoide/tratamiento farmacológico , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Ratones , Albúmina Sérica Humana/química , Albúmina Sérica Humana/administración & dosificación , Masculino , Sinergismo Farmacológico , Humanos , Portadores de Fármacos/química , Artritis Experimental/tratamiento farmacológico
3.
Balkan Med J ; 40(1): 40-50, 2023 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-36472091

RESUMEN

Background: As one of the adverse events after hip fracture surgery, hypoalbuminemia is usually treated using human serum albumin infusion. However, the application of human serum albumin may cause complications such as postsurgical infection and increased mortality. Aims: To examine the preoperative risk factors of human serum albumin infusion after hip fracture surgery, establish a nomogram prediction model, and verify its accuracy. Study Design: A retrospective cross-sectional study. Methods: Eligible patients who underwent hip fracture surgery were divided into the infusion and non-infusion groups according to whether human serum albumin was infused or not. All patients were divided randomly into a training set and a testing set in line with the ratio of 7:3. In the training set, independent risk factors of postoperative human serum albumin infusion were determined by univariate logistic regression analysis, LASSO regression, and multivariate logistic regression analysis. Then, a nomogram model was established. Furthermore, the receiver operating characteristic curve and calibration curve were plotted, and decision curve analysis was performed for the training and testing sets to assess the predictability, discriminative ability, and clinical usefulness of the model. Results: This study included a total of 1,339 eligible patients, 141 of whom were injected with human serum albumin postoperatively. Altogether, the training set incorporated 939 patients, and the testing set included 400 patients. Multivariate logistic analysis indicated five independent risk factors, including chronic lung disease (odds ratio, 95% confidence interval, 2.618, 1.413-4.849, p = 0.002), (albumin; odds ratio, 95% confidence interval, 0.842, 0.787-0.900, p < 0.001), prothrombin time (odds ratio, 95% confidence interval, 1.252, 1.071-1.463, p = 0.005), red blood cells (odds ratio, 95% confidence interval, 0.370, 0.228-0.602, p < 0.001), and type of anesthesia (odds ratio, 95% confidence interval, 0.553, 0.327-0.937, p = 0.028). Fracture type, a clinically significant factor, was also considered. Finally, the nomogram model was built based on these seven predictors. The areas under the curve of the nomogram were 0.854 (95% confidence interval, 0.811-0.898) and 0.767 (95% confidence interval, 0.686-0.847) in the training and testing sets separately. As shown in the calibration curve, the predicted result was consistent with the observed one. The decision curve analysis indicated that the nomogram has good clinical value. Conclusion: Low preoperative serum albumin levels, low preoperative red blood cell counts, prolonged preoperative prothrombin time, history of chronic lung disease, and general anesthesia were independent risk factors for postoperative human serum albumin infusion. Besides, the fracture type, clinically significant factor, was also included. The nomogram that combined these six predictors could accurately predict the risk of postoperative human serum albumin infusion.


Asunto(s)
Fracturas de Cadera , Nomogramas , Complicaciones Posoperatorias , Albúmina Sérica Humana , Humanos , Estudios Transversales , Enfermedades Pulmonares , Estudios Retrospectivos , Factores de Riesgo , Albúmina Sérica Humana/administración & dosificación , Fracturas de Cadera/cirugía
4.
World Neurosurg ; 157: e374-e389, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34662656

RESUMEN

BACKGROUND: There have been few literature reports on the use of perioperative parameters to predict the risk of albumin transfusion after spinal tuberculosis surgery based on the application of nomogram and propensity score matching (PSM) analysis. OBJECTIVE: The purpose was to predict the risk of albumin transfusion after spinal tuberculosis surgery based on a combination of PSM and nomogram. METHODS: The clinical data of the patients were collected in our hospital, including preoperative clinical data, preoperative laboratory tests, and postoperative clinical data. All data were divided into 2 groups, including the albumin transfusion group and the non-albumin transfusion group. The PSM analysis was used to adjust the baseline data of the 2 groups. The nomogram was further constructed. The practicability and predictive ability of the model were evaluated. RESULTS: A total of 494 cases were collected in this article; 102 pairs by PSM analysis were used to construct the nomogram. There were statistical differences in surgical approach, aspartate aminotransferase/alanine aminotransferase levels, drainage, and kyphosis by logistic analysis, and these parameters were included in the construction of the nomogram. The C-index of the prediction model was 0.734. The area under the curve was 0.73 and the net benefit was between 0.13 and 0.99. The calculated C-index was 0.71 by the internal verification method. CONCLUSIONS: The PSM analysis had a good matching effect and the nomogram had a good predictive ability. Surgical approach, aspartate aminotransferase/alanine aminotransferase levels, drainage, and kyphosis might be predictors of albumin transfusion after spinal tuberculosis surgery.


Asunto(s)
Transfusión de Eritrocitos/tendencias , Nomogramas , Puntaje de Propensión , Albúmina Sérica Humana/administración & dosificación , Tuberculosis de la Columna Vertebral/diagnóstico por imagen , Tuberculosis de la Columna Vertebral/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Factores de Riesgo , Adulto Joven
5.
Pharm Res ; 38(6): 1011-1030, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34080101

RESUMEN

PURPOSE: A multiphysics simulation model was recently developed to capture major physical and mechanical processes of local drug transport and absorption kinetics of subcutaneously injected monoclonal antibody (mAb) solutions. To further explore the impact of individual drug attributes and tissue characteristics on the tissue biomechanical response and drug mass transport upon injection, sensitivity analysis was conducted and reported. METHOD: Various configurations of injection conditions, drug-associated attributes, and tissue properties were simulated with the developed multiphysics model. Simulation results were examined with regard to tissue deformation, porosity change, and spatiotemporal distributions of pressure, interstitial fluid flow, and drug concentration in the tissue. RESULTS: Injection conditions and tissue properties were found influential on the mechanical response of tissue and interstitial fluid velocity to various extents, leading to distinct drug concentration profiles. Intrinsic tissue porosity, lymphatic vessel density, and drug permeability through the lymphatic membrane were particularly essential in determining the local absorption rate of an mAb injection. CONCLUSION: The sensitivity analysis study may shed light on the product development of an mAb formulation, as well as on the future development of the simulation method.


Asunto(s)
Factores Biológicos/metabolismo , Simulación por Computador , Modelos Biológicos , Albúmina Sérica Humana/metabolismo , Absorción Cutánea/fisiología , Tejido Subcutáneo/metabolismo , Factores Biológicos/administración & dosificación , Fenómenos Biomecánicos/efectos de los fármacos , Fenómenos Biomecánicos/fisiología , Humanos , Inyecciones Subcutáneas , Albúmina Sérica Humana/administración & dosificación , Absorción Cutánea/efectos de los fármacos , Tejido Subcutáneo/efectos de los fármacos
6.
Sci Rep ; 11(1): 10834, 2021 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-34035380

RESUMEN

Fluid resuscitation following severe inflammation-induced hypoperfusion is critical for the restoration of hemodynamics and the prevention of multiorgan dysfunction syndrome during septic shock. Fluid resuscitation with commercially available crystalloid and colloid solutions only provides transient benefits, followed by fluid extravasation and tissue edema through the inflamed endothelium. The increased molecular weight (M.W.) of polymerized human serum albumin (PolyHSA) can limit fluid extravasation, leading to restoration of hemodynamics. In this prospective study, we evaluated how fluid resuscitation with PolyHSA impacts the hemodynamic and immune response in a lipopolysaccharide (LPS) induced endotoxemia mouse model. Additionally, we evaluated fluid resuscitation with PolyHSA in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Resuscitation with PolyHSA attenuated the immune response and improved the maintenance of systemic hemodynamics and restoration of microcirculatory hemodynamics. This decrease in inflammatory immune response and maintenance of vascular wall shear stress likely contributes to the maintenance of vascular integrity following fluid resuscitation with PolyHSA. The sustained restoration of perfusion, decrease in pro-inflammatory immune response, and improved vascular integrity that results from the high M.W. of PolyHSA indicates that a PolyHSA based solution is a potential resuscitation fluid for endotoxic and septic shock.


Asunto(s)
Endotoxemia/tratamiento farmacológico , Fluidoterapia/métodos , Microcirculación/efectos de los fármacos , Albúmina Sérica Humana/administración & dosificación , Choque Séptico/tratamiento farmacológico , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Endotoxemia/inducido químicamente , Endotoxemia/inmunología , Regulación de la Expresión Génica/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Lipopolisacáridos/efectos adversos , Masculino , Mesocricetus , Ratones , Estudios Prospectivos , Albúmina Sérica Humana/farmacología , Choque Séptico/etiología , Choque Séptico/inmunología
7.
ACS Appl Mater Interfaces ; 13(11): 12888-12898, 2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33715358

RESUMEN

With the gradual deep understanding of the tumorigenesis and development process, nanodrug are thought to have great prospects for individualized treatment of tumors. To deliver adequate concentration of active ingredients to targeted tissues, proteins are usually used as carriers to avoid clearance by the immune system. Herein, a new strategy is developed for preparation of the protein-functionalized targeting nanodrugs; different kinds of proteins (albumin, horseradish, transferrin, and ricin) can be quickly loaded in polyacrylic acid nanohydrogels (PAA-NGs) without discrimination within 1 min under the strong driving force of entropy; and the loading efficiency can reach 99% with about 50% loading content. Meanwhile, the activity of the released protein can be well retained. After oriented binding of the targeting agent on the surface of the nanocarriers by a unique and facile technique, the protein-loaded nanodrug exhibits excellent tumor cell uptake and targeting effect. The excellent targeting ability from the oriented binding is further proved by comparing with the non-oriented targeting system. With quick loading of the anti-tumor protein of ricin and oriented binding of transferrin protein (Tf), the targeting nanodrug (PAA-BB@Ricin/Tf) shows a remarkable anti-tumor effect. This study proves a new universal delivery and targeting strategy for improving the nanodelivery system, which has great potentials for clinical application.


Asunto(s)
Resinas Acrílicas/química , Portadores de Fármacos/química , Hidrogeles/química , Neoplasias/tratamiento farmacológico , Proteínas/administración & dosificación , Animales , Sistemas de Liberación de Medicamentos , Entropía , Células Hep G2 , Humanos , Ratones Endogámicos ICR , Ratones Desnudos , Nanoestructuras/química , Neoplasias/patología , Proteínas/farmacocinética , Proteínas/uso terapéutico , Ricina/administración & dosificación , Ricina/farmacocinética , Albúmina Sérica Humana/administración & dosificación , Albúmina Sérica Humana/farmacocinética , Albúmina Sérica Humana/uso terapéutico , Transferrina/administración & dosificación , Transferrina/farmacocinética , Transferrina/uso terapéutico
8.
Hepatology ; 74(5): 2848-2862, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33772846

RESUMEN

Human serum albumin is the most abundant plasma protein, and it regulates diverse body functions. In patients with advanced and decompensated cirrhosis, serum albumin levels are low because of a reduction in the hepatocyte mass due to disease per se and multiple therapeutic interventions. Because of their oncotic and nononcotic properties, administration of human albumin solutions (HAS) have been found to be beneficial in patients undergoing large-volume paracentesis or who have hepatorenal syndrome or spontaneous bacterial peritonitis. Albumin also improves the functionality of the immune cells and mitigates the severity and risk of infections in advanced cirrhosis. Its long-term administration can modify the course of decompensated cirrhosis patients by reducing the onset of new complications, improving the quality of life, and probably providing survival benefits. There is, however, a need to rationalize the dose, duration, and frequency of albumin therapy in different liver diseases and stages of cirrhosis. In patients with acute-on-chronic liver failure, potentially toxic oxidized isoforms of albumin increase substantially, especially human nonmercaptalbumin and 2, and nitrosoalbumin. The role of administration of HAS in such patients is unclear. Determining whether removal of the pathological and dysfunctional albumin forms in these patients by "albumin dialysis" is helpful, requires additional studies. Use of albumin is not without adverse events. These mainly include allergic and transfusion reactions, volume overload, antibody formation and coagulation derangements. Considering their cost, limited availability, need for a health care setting for their administration, and potential adverse effects, judicious use of HAS in liver diseases is advocated. There is a need for new albumin molecules and economic alternatives in hepatologic practice.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Síndrome Hepatorrenal/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Albúmina Sérica Humana/administración & dosificación , Insuficiencia Hepática Crónica Agudizada/sangre , Trastornos de la Coagulación Sanguínea/inducido químicamente , Trastornos de la Coagulación Sanguínea/epidemiología , Relación Dosis-Respuesta a Droga , Síndrome Hepatorrenal/sangre , Síndrome Hepatorrenal/etiología , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Albúmina Sérica Humana/efectos adversos , Albúmina Sérica Humana/análisis , Reacción a la Transfusión/epidemiología , Reacción a la Transfusión/etiología , Resultado del Tratamiento
9.
Mol Neurobiol ; 58(7): 3031-3042, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33608826

RESUMEN

Parkinson's disease is the most common neurodegenerative movement disorder with unclear etiology and only symptomatic treatment to date. Toward the development of novel disease-modifying agents, neurotrophic factors represent a reasonable and promising therapeutic approach. However, despite the robust preclinical evidence, clinical trials using glial-derived neurotrophic factor (GDNF) and neurturin have been unsuccessful. In this direction, the therapeutic potential of other trophic factors in PD and the elucidation of the underlying molecular mechanisms are of paramount importance. The liver growth factor (LGF) is an albumin-bilirubin complex acting as a hepatic mitogen, which also exerts regenerative effects on several extrahepatic tissues including the brain. Accumulating evidence suggests that intracerebral and peripheral administration of LGF can enhance the outgrowth of nigrostriatal dopaminergic axonal terminals; promote the survival, migration, and differentiation of neuronal stem cells; and partially protect against dopaminergic neuronal loss in the substantia nigra of PD animal models. In most studies, these effects are accompanied by improved motor behavior of the animals. Potential underlying mechanisms involve transient microglial activation, TNF-α upregulation, and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) and of the transcription factor cyclic AMP response-element binding protein (CREB), along with anti-inflammatory and antioxidant pathways. Herein, we summarize recent preclinical evidence on the potential role of LGF in PD pathogenesis, aiming to shed more light on the underlying molecular mechanisms and reveal novel therapeutic opportunities for this debilitating disease.


Asunto(s)
Bilirrubina/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Albúmina Sérica Humana/metabolismo , Animales , Bilirrubina/administración & dosificación , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Vías de Administración de Medicamentos , Humanos , Albúmina Sérica Humana/administración & dosificación , Sustancia Negra/efectos de los fármacos , Sustancia Negra/metabolismo
10.
Pharm Dev Technol ; 26(1): 1-10, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32985928

RESUMEN

The use of chemotherapeutic drug paclitaxel (PTX) for the treatment of tumors has several limitations, including multidrug resistance (MDR) and serious adverse reactions. This research aims to co-encapsulate PTX and the chemosensitizer 2-methoxyestradiol (2-ME) into folate-conjugated human serum albumin nanoparticles (FA-HSANPs) to reduce multiple drug resistance and improve antitumor efficiency. The results show PTX/2-ME@FA-HSANPs had uniform particle size (180 ± 12.31 nm) and high encapsulation efficacy. It also exhibited highly potent cytotoxicity and apoptosis-inducing activities in the G2/M phase of PTX-resistant EC109/Taxol cells. Moreover, PTX/2-ME@FA-HSANPs not only displayed better inhibition of tumor growth in S-180 tumor-bearing mice than PTX alone but also reduced pathological damage to normal tissues. In summary, PTX/2-ME@FA-HSANPs could be a promising vehicle for tumor therapy and reducing drug resistance. This research will also provide references for other MDR treatment.


Asunto(s)
2-Metoxiestradiol/administración & dosificación , Resistencia a Antineoplásicos/efectos de los fármacos , Ácido Fólico/administración & dosificación , Nanopartículas/administración & dosificación , Paclitaxel/administración & dosificación , Albúmina Sérica Humana/administración & dosificación , Animales , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Línea Celular Tumoral , Portadores de Fármacos/administración & dosificación , Resistencia a Antineoplásicos/fisiología , Femenino , Humanos , Ratones , Ratas , Ratas Sprague-Dawley , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
11.
J Hepatol ; 74(2): 340-349, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32853747

RESUMEN

BACKGROUND & AIMS: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. METHODS: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score. RESULTS: Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5-4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal. CONCLUSION: Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin - 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration. LAY SUMMARY: The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.


Asunto(s)
Ascitis , Cirrosis Hepática , Cuidados a Largo Plazo/métodos , Albúmina Sérica Humana/administración & dosificación , Albúmina Sérica/análisis , Ascitis/etiología , Ascitis/terapia , Productos Biológicos/administración & dosificación , Biomarcadores Farmacológicos/análisis , Monitoreo de Drogas/métodos , Femenino , Humanos , Análisis de Intención de Tratar , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Cirrosis Hepática/mortalidad , Cirrosis Hepática/terapia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Análisis de Supervivencia , Resultado del Tratamiento
12.
Drug Res (Stuttg) ; 71(1): 10-16, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33022718

RESUMEN

The efficacy of albumin and fresh frozen plasma (FFP) and their effects on biomarkers of oxidative stress has been evaluated. In a randomized clinical control trial, 33 poisoned patients by Organophosphate (OP) were enrolled in the research and divided into three groups. The first group underwent conventional treatments by atropine and pralidoxime (control group); the second and third groups, in addition to traditional treatments, received albumin and FFP. Cholinesterase (ChE) enzyme activity, total antioxidant capacity (TAC), serum thiol groups (TTG), malonyl aldehyde (MDA) and DNA damage were measured in all treatment and control groups. Patients were matched in terms of demographic characteristics at the beginning of the study. ChE activity was increased in all three groups during treatment, which was more noticeable in the FFP group and was statistically significant in both albumin and FFP group compared to the control group (p<0.05). TAC increased, and TTG decreased in FFP and albumin groups compared to the control group; no significant difference was observed. MDA decreased in albumin and FFP and was significantly different in the FFP group compared to the control group (p<0.05). The amount of DNA damage in FFP and albumin groups decreased, and there was a significant difference compared to the control group (p<0.05). According to the results of this study, due to the decrease of oxidative damage parameters and the increase of antioxidant parameters in albumin and specially FFP groups, FFP may be considered as an adjunctive treatment for OP poisoning.


Asunto(s)
Daño del ADN/efectos de los fármacos , Intoxicación por Organofosfatos/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Plasma , Albúmina Sérica Humana/administración & dosificación , Adulto , Biomarcadores/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intoxicación por Organofosfatos/diagnóstico , Resultado del Tratamiento , Adulto Joven
14.
Toxicology ; 449: 152662, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33359713

RESUMEN

Given significant species-specific differences in liver functions, cultures of primary human hepatocytes (PHHs) are useful for assessing drug metabolism and to mitigate the risk of drug-induced hepatotoxicity in humans. While significant advances have been made to keep PHHs highly functional for 2-4 weeks in vitro, especially upon co-culture with both liver- and non-liver-derived non-parenchymal cells (NPCs), the functional lifespan of PHHs is 200-400 days in vivo. Therefore, it is desirable to determine culture conditions that can further prolong PHHs functions in vitro for modeling chronic drug exposure, disease pathogenesis, and to provide flexibility to the end-user for staggering drug incubations across multiple culture batches. Most PHH culture platforms utilize supraphysiologic levels of glucose and insulin and bovine-derived serum when including NPCs, which can alter PHH functions. Therefore, here we developed a culture medium containing physiologic levels of glucose (5 mM), insulin (500 pM), and human serum (10 % v/v) and tested its effects on micropatterned co-cultures (MPCCs) in which PHHs are organized onto collagen domains of empirically optimized dimensions and surrounded by 3T3-J2 murine fibroblasts that express liver-like molecules and induce higher PHH functions than liver-derived NPCs. Our physiologically-inspired culture medium allowed better retention of PHH morphology, polarity, and functions (albumin and urea, cytochrome-P450 activities, and sensitivity to insulin-mediated inhibition of gluconeogenesis) for up to 10 weeks relative to the traditional medium. Finally, PHHs in the physiologic medium displayed clinically-relevant responses to prototypical drugs for hepatoxicity and cytochrome-P450 induction. Ultimately, our physiologic culture medium could find broader utility for the continued development of PHH-NPC co-cultures for drug development, investigating the effects of patient-derived sera on PHH functions and disease phenotypes, and for use in cell-based therapies.


Asunto(s)
Técnicas de Cocultivo/métodos , Medios de Cultivo/farmacología , Glucosa/administración & dosificación , Hepatocitos/fisiología , Insulina/administración & dosificación , Albúmina Sérica Humana/administración & dosificación , Adulto , Animales , Bovinos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Femenino , Hepatocitos/efectos de los fármacos , Humanos , Resistencia a la Insulina/fisiología , Masculino , Persona de Mediana Edad
16.
Pediatr Nephrol ; 35(10): 1985-1990, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32377865

RESUMEN

Congenital nephrotic syndrome (CNS) was primarily considered one disease entity. Hence, one treatment protocol was proposed in the beginning to all CNS patients. Today, with the help of gene diagnostics, we know that CNS is a heterogeneous group of disorders and therefore, different treatment protocols are needed. The most important gene defects causing CNS are NPHS1, NPHS2, WT1, LAMB2, and PLCE1. Before active treatment, all infants with CNS died. It was stated already in the mid-1980s that intensive medical therapy followed by kidney transplantation (KTx) should be the choice of treatment for infants with severe CNS. In Finland, early aggressive treatment protocol was adopted from the USA and further developed for treatment of children with the Finnish type of CNS. The aim of this review is to state reasons for "early aggressive treatment" including daily albumin infusions, intensified nutrition, and timely bilateral nephrectomy followed by KTx at the age of 1-2 years.


Asunto(s)
Trasplante de Riñón , Nefrectomía , Síndrome Nefrótico/terapia , Apoyo Nutricional/métodos , Albúmina Sérica Humana/administración & dosificación , Humanos , Lactante , Infusiones Intravenosas , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/genética , Síndrome Nefrótico/mortalidad , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tiempo de Tratamiento , Resultado del Tratamiento
17.
Pediatr Nephrol ; 35(10): 1991-1996, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32462257

RESUMEN

The management of infants with congenital nephrotic syndrome (CNS) is very challenging as they are prone to severe complications such as hemodynamic disturbances, infections, thromboses, and impaired growth, and most will develop end-stage kidney disease (ESKD) within a few years. Since the seventies, an "aggressive" approach, including daily albumin infusions, early nephrectomies, dialysis, and transplantation, has dramatically improved survival and morbidity. More recent case-note reviews have reported successful conservative treatment (using optimized nutrition, complication prophylaxis, and delayed renal replacement therapy), which led to similarly good outcomes and low complication rates. This questions the indications for early preemptive bilateral nephrectomy and dialysis given the mortality and morbidity rates in dialysis in infants and their life-long management with possible repeated transplantations. Two large series provide the most recent evidences supporting the conservative management: firstly, at least 55% children with CNS are not spontaneously in ESKD at the age of 2 years; secondly, albumin tapering/discontinuation and hospital discharge are possible before nephrectomy; and lastly, CNS complication rates are similar in case of preemptive nephrectomies or conservative care. Until now, no clear genotype-phenotype correlation has been identified to guide clinical management. Taken together, these data support the safety of conservative care until ESKD in a subset of patients with CNS.


Asunto(s)
Tratamiento Conservador/métodos , Fallo Renal Crónico/epidemiología , Nefrectomía/efectos adversos , Síndrome Nefrótico/terapia , Terapia de Reemplazo Renal/efectos adversos , Progresión de la Enfermedad , Humanos , Lactante , Infusiones Intravenosas , Fallo Renal Crónico/patología , Fallo Renal Crónico/prevención & control , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/mortalidad , Síndrome Nefrótico/patología , Apoyo Nutricional/efectos adversos , Apoyo Nutricional/métodos , Albúmina Sérica Humana/administración & dosificación , Albúmina Sérica Humana/efectos adversos , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tiempo de Tratamiento
18.
Daru ; 28(1): 209-219, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32270402

RESUMEN

BACKGROUND: Many solutions have been evaluated to deal with "chemotherapy and radiation-resistant cancer cells' as well as "severe complications of chemotherapy drugs". One of these solutions is the use of herbal compounds with antioxidant properties. Among these antioxidant compounds, curcumin is identified as the strongest one to inhibit cancerous cells proliferation. However, its clinical trials have encountered many constraints, because curcumin is insoluble in water and unstable in physiological conditions. To overcome these limitations, in this study, curcumin was conjugated with human serum albumin (HSA) and its effects on breast cancer cell lines were also measured. METHODS: After making of HSA-curcumin nanoparticles (NPs) by the desolvation technique, they were characterized by the FTIR, DLS, TEM, and SEM method. At the end, its anticancer effects have been examined using MTT test and apoptosis assay. RESULTS: The FTIR graph confirmed that curcumin and HSA have been conjugated along with each other. Particles size was reported to be 220 nm and 180 nm by DLS and SEM, respectively. The zeta potential of HSA-curcumin NPs was -7 mV, while it was -37 mV for curcumin. The MTT and apoptosis assay results indicated that the toxicity of HSA-curcumin NPs on the normal cell are less than curcumin; however, its anti-cancer effects on the cancer cells are much greater, compared to curcumin. CONCLUSION: HSA-curcumin NPs increase curcumin solubility in water as well as its stability in physiological and acidic conditions. These factors have the ability of overwhelming the limitations on using curcumin alone, and they could result in a significant increase in the toxicity of curcumin on the cancer cells without increasing its toxicity on the normal cells. Grapical abstract.


Asunto(s)
Anticarcinógenos/administración & dosificación , Antineoplásicos/administración & dosificación , Curcumina/administración & dosificación , Portadores de Fármacos/administración & dosificación , Nanopartículas/administración & dosificación , Albúmina Sérica Humana/administración & dosificación , Anticarcinógenos/química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Curcumina/química , Portadores de Fármacos/química , Liberación de Fármacos , Humanos , Nanopartículas/química , Neoplasias/prevención & control , Albúmina Sérica Humana/química
19.
United European Gastroenterol J ; 8(5): 528-535, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32213034

RESUMEN

Albumin is currently employed as a plasma expander to prevent and treat specific complications of cirrhosis with ascites, such as the prevention of paracentesis-induced circulatory dysfunction and renal dysfunction induced by spontaneous bacterial peritonitis, as well as the diagnosis and treatment of acute kidney injury and hepatorenal syndrome. Recently, evidence has shown that long-term albumin administration in patients with decompensated cirrhosis reduces mortality and incidence of complications, eases the management of ascites, is cost effective, and has a good safety profile.


Asunto(s)
Lesión Renal Aguda/prevención & control , Ascitis/terapia , Síndrome Hepatorrenal/prevención & control , Cirrosis Hepática/terapia , Peritonitis/prevención & control , Albúmina Sérica Humana/administración & dosificación , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Anciano , Ascitis/diagnóstico , Ascitis/etiología , Enfermedad Crónica/terapia , Diuréticos/administración & dosificación , Esquema de Medicación , Femenino , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/etiología , Humanos , Infusiones Intravenosas , Recuento de Leucocitos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Paracentesis , Peritonitis/diagnóstico , Peritonitis/etiología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
20.
Artículo en Inglés, Español | MEDLINE | ID: mdl-32201272

RESUMEN

OBJECTIVE: To optimize radiolabeling with 99mTc and 67Ga of albumin nanoparticles coated with 4 differents synthetic polymers and to evaluate their stability in vivo and in vitro, as well as their biodistribution in vivo after intravenous administration. MATERIAL AND METHODS: The nanoparticles were prepared using albumin and NOTA-modified albumin by the desolvation method and coated with 4 different polymers; HPMC, GMN2, GPM2 and GTM2. They were purified, lyophilized and characterized. Radiolabelling with 99mTc was perfomed with 74 MBq of 99mTc sodium pertechnetate, previously reduced with and acid solution of tin chloride at different concentrations (0.003, 0.005, 0.007, 0.01, 0.05 and 0.1mg/ml) and at different times (5, 10, 15, 30 and 60minutes) and temperatures (room temperature, 40°C and 60°C). Radiolabelling with 67Ga was perfomed by incubation of the nanoparticles with 37 MBq of 67Gallium chloride (obtained from commercial gallium-67 citrate) at different times (10 and 30minutes) and temperatures (room temperature, 30°C and 60°C), and posterior purification with microconcentrators. The radiochemical purity was evaluated by TLC. Stability studies of radiolabeled nanoparticles in physiological serum and blood plasma were perfomed. Biodistribution studies of nanoparticles coated with GPM2 polymer were carried out in Wistar rats after intravenous administration of the nanoparticles. Control animals were carried out with 99mTc sodium pertechnetate and 67Ga chloride. To do so, the animals were killed and activity in organs was measured in a gamma counter. RESULTS: 99mTc labeling was carried out optimally with a tin concentration of 0.007mg/ ml for the GPM2 nanoparticles and 0.005mg / ml for the rest of the formulations, with a radiolabelling time of 10minutes at room temperature. In the case of 67Ga the label was optimized at 30° C temperature and 30minutes of incubation. In both cases the radiochemical purity obtained was greater than 97%. The nanoparticles showed high stability in vitro after 48hours of labeling (70% nanoparticles labeled with 99mTc and 90% those labeled with 67Ga). Biodistribution studies of nanoparticles 99mTc -GPM2 and 67Ga -NOTA-GPM2 showed a high accumulation of activity in the liver at 2 and 24hours after intravenous administration. CONCLUSION: The labeling procedure with 99mTc and 67Ga of albumin and albumin modified with NOTA nanoparticles allows obtaining nanoparticles with high labeling yields and adequate in vitro stability, allowing their use for in vivo studies.


Asunto(s)
Radioisótopos de Galio/farmacocinética , Galio/farmacocinética , Marcaje Isotópico/métodos , Nanopartículas/administración & dosificación , Poliaminas/química , Radiofármacos/farmacocinética , Albúmina Sérica Humana/farmacocinética , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , Tecnecio/farmacocinética , Tiamina/química , Animales , Cromatografía en Capa Delgada , Estabilidad de Medicamentos , Femenino , Galio/administración & dosificación , Galio/análisis , Radioisótopos de Galio/administración & dosificación , Radioisótopos de Galio/análisis , Compuestos Heterocíclicos con 1 Anillo , Derivados de la Hipromelosa , Inyecciones Intravenosas , Nanopartículas/análisis , Polietilenglicoles , Radiofármacos/administración & dosificación , Radiofármacos/análisis , Ratas , Ratas Wistar , Albúmina Sérica Humana/administración & dosificación , Albúmina Sérica Humana/análisis , Tecnecio/administración & dosificación , Tecnecio/análisis , Temperatura , Compuestos de Estaño , Distribución Tisular
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